FGFR Inhibitor

Surfen dihydrochloride is a potent heparan sulfate antagonist. Surfen inhibits FGF2 binding and signal transduction. Surfen binds to glycosaminoglycans and reduces tau hyperphosphorylation. Surfen dihydrochloride inhibits the activity of recombinant uronyl 2-O-sulfotransferase with an IC₅₀ of approximately 2 μM. Surfen dihydrochloride inhibits HSV-1 viral infection. Surfen dihydrochloride inhibits neural differentiation, delays remyelination, and alleviates EAE.

Masitinib (AB1010) is a potent, orally bioavailable, and selective inhibitor of c-Kit (IC₅₀=200 nM for human recombinant c-Kit). It also inhibits PDGFRα/β (IC₅₀s=540/800 nM), Lyn (IC₅₀= 510 nM for LynB), Lck, and, to a lesser extent, FGFR3 and FAK. Masitinib (AB1010) has anti-proliferative, pro-apoptotic activity and low toxicity.

Dovitinib (CHIR-258) is an orally active, potent multi-targeted tyrosine kinase (RTK) inhibitor with IC₅₀s of 1, 2, 36, 8/9, 10/13/8, 27/210 nM for FLT3, c-Kit, CSF-1R, FGFR1/FGFR3, VEGFR1/VEGFR2/VEGFR3 and PDGFRα/PDGFRβ, respectively. Dovitinib has potent antitumor activity.

PD166866 is a selective FGFR1 tyrosine kinase inhibitor with an IC₅₀ of 52.4 nM.

BLU9931 is a potent, highly selective, and irreversible fibroblast growth factor receptor 4 (FGFR4) inhibitor with an IC₅₀ of 3 nM and a K_d of 6 nM. BLU9931 has significant antitumor activity.

Fisogatinib (BLU-554) is a potent, highly selective and orally active fibroblast growth factor receptor 4 (FGFR4) inhibitor with an IC₅₀ of 5 nM. Fisogatinib has significant anti-tumor activity in models of hepatocellular carcinoma (HCC) that are dependent on FGFR4 signalling.

KW-2449 is a multi-targeted kinase inhibitor of FLT3, ABL, ABL^T315I and Aurora kinase with IC₅₀s of 6.6, 14, 4 and 48 nM, respectively.

Vosoritide (BMN 111) acetate is a natriuretic peptide receptor 2 (NPR2) agonist that acts on the proliferation and differentiation of chondrocytes to promote bone growth.

Bemarituzumab is a humanized IgG1 monoclonal antibody against FGFR2b (a FGF receptor). Bemarituzumab blocks fibroblast growth factors from binding and activating FGFR2b. Bemarituzumab has antitumor activity against gastric and breast cancer.

Derazantinib (ARQ-087) is an ATP competitive and orally activeFGFR inhibitor (IC₅₀s: 1.8 nM for FGFR2, 4.5 nM for FGFR1 and 3 nM). Derazantinib inhibits FGFR phosphorylation. Derazantinib inhibits tumor growth in multiple xenograft models.

Ponatinib hydrochloride (AP24534 hydrochloride) is a hydrochloride of ponatinib. Ponatinib is an orally active multi-targeted kinase inhibitor with IC₅₀s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.

PF 477736 (PF 00477736) is a potent, selective and ATP-competitive inhibitor of Chk1, with a K_i of 0.49 nM, it is also a Chk2 inhibitor, with a K_i of 47 nM. PF 477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3, and Ret (IC₅₀=8 (K_i), 10, 14, 23, 23, 25, and 39 nM, respectively). PF 477736 can enhance Gemcitabine antitumor activity in vitro and in vivo.

Roblitinib (FGF-401) is an orally active and highly selective FGFR4 inhibitor with an IC₅₀ of 1.9 nM. Roblitinib has antitumor activity.

Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC₅₀ of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC₅₀ of 4, 25, 32, 44, and 95 nM.

CEP-11981(ESK981; BOL 303213X) is an orally active tyrosine kinase inhibitor (TKI), which can target TIE2, VEGFR1-3 and FGFR1, and has potential anti-tumor and anti-angiogenic effects.

SM1-71 (compound 5) is a potent TAK1 inhibitor, with a K_i of 160 nM, it also can covalently inhibit MKNK2, MAP2K1/2/3/4/6/7, GAK, AAK1, BMP2K, MAP3K7, MAPKAPK5, GSK3A/B, MAPK1/3, SRC, YES1, FGFR1, ZAK (MLTK), MAP3K1, LIMK1 and RSK2. SM1-71 can inhibit proliferation of multiple cancer cell lines.

Regorafenib (BAY 73-4506) monohydrate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC₅₀ values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib monohydrate shows very robust antitumor and antiangiogenic activity.

Pazopanib Hydrochloride (GW786034 Hydrochloride) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with an IC₅₀ of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.

Dabogratinib (TYRA-300) is an orally active, selective FGFR3 inhibitor with an IC₅₀ of 11 nM. Dabogratinib exhibits antitumor activity against urothelial carcinoma and solid tumors. Dabogratinib downregulates the FGFR3 and ERK1/2 signaling pathways, and induces tumor growth inhibition and regression in FGFR3-altered xenograft models. Dabogratinib promotes chondrocyte proliferation and differentiation, drives endochondral bone formation and overall body growth, partially restores long bone proportions, and improves craniofacial and spinal morphology. Dabogratinib can be used for the research of metastatic urothelial carcinoma, achondroplasia and hypochondroplasia.

Orantinib (SU6668; TSU-68) is a multi-targeted receptor tyrosine kinase inhibitor with K_is of 2.1 μM, 8 nM and 1.2 μM for Flt-1, PDGFRβ and FGFR1, respectively.